Lecture 1 - General Properties of Amino Acids(2) (1).pdf

1
BCM 251 INTRODUCTION TO PROTEINS
Lecture 1: General
Properties of Amino Acids
Prof Oleg Reva
oleg.reva@up.ac.za
Chapters 3.1

Protein and amino acids’ facts
2
Proteins
Proteins serve as basic structural molecules of all cells and tissues of living
organisms. Proteins make up nearly 17% of the total body weight. There are
90-140 million molecules of proteins per one yeast cell; or up to 1010
proteins per one mammalian cell.
To understand role and function of a protein, it is important to know its basic
structure and composition.
Amino acids
Amino acids are fundamental building blocks of proteins. Long linear chains
of amino acids, called polypeptides, make up proteins and determine their
structure, properties and functions. Amino acids are built of the following
elements: carbon, hydrogen, oxygen, nitrogen, and sometimes, sulfur.
Residues
In proteins, each amino acid residue joined to its neighbour by a specific
type of covalent bonds termed peptide bond. The term residue reflects a
loss of a water molecule (dehydration reaction) when one amino acid is
joined to another forming the peptide bond.

Amino acid structure
3
Amino acids
The general structure of amino acids consists of a carbon centre
termed an -carbon atom and four substituents linked to this atom,
which are: one amino group (NH2 → NH3
+), one carboxyl group
(COOH → COO−), a hydrogen atom (H), and a fourth group, referred
to as the R-group or side radical, that determines the structural
identity and chemical properties of individual amino acids.
The first three groups are common to all amino acids. The basic
amino acid structure is R-CH(NH2)-COOH or NH3
+-RCH-COO− (both
variants are correct)

General properties
of amino acids
4

Properties of amino acids
5
➢ All amino acids share several common chemical properties
because all of possessing the following functional groups:
• One alpha-amino group;
• One alpha-carboxyl group;
➢ Several common properties can be explained by the presence of
both these radicals, alpha-amino group and alpha-carboxyl group,
attached to the same carbon atom.
➢ Side radicals of amino acids bear other functional groups (aliphatic
chains, aromatic rings, hydroxyl groups and additional amino and
carboxyl groups), which are specific for every amino acid.
Side radicals determine the individual properties of amino acids.
You have to be able to tell difference between common and individual
properties of amino acids and be able to explain these properties by the
presence of functional groups responsible for these properties.

6
Properties of amino acids due to carboxyl group
◼ Salt formation. Amino acids are organic acids and may
form salts with many cations, particularly with hydroxides:
◼ Reaction with alcohols (esterification).
◼ Reaction with amines to form amides.

7
Properties of amino acids due to carboxyl group
◼ Decarboxylation. Amino acids may undergo alpha
decarboxylation to form the corresponding amines. This is a
natural pathway of biosynthesis of many important amines
produced from amino acids in living organisms:
➢ Histidine → Histamine + CO2 (local immune response);
➢ Tyrosine → Tyramine + CO2 (role in blood-brain barrier);
➢ Tryptophan → Tryptamine + CO2 (neurotransmitter);
➢ Glutamic acid → g-amino butyric acid (GABA) + CO2
(neurotransmitter);
➢ Lysine → Cadaverine + CO2 (toxin – is created spontaneously in
dead bodies. In contrast to other reactions shown above,
cadaverine formation is not controlled by any enzymes, whereas all
other reactions shown above are catalyzed by specific enzymes);

8
Properties of amino acids due to amino group
◼ Reaction with mineral acids.
R-CH(NH2)-COOH + HCl = [R-CH(NH+
3)-COOH]Cl−
◼ Reaction with benzaldehyde.
Schiff’s base formation is an intermediate step of all
transamination reactions – an important part of the
biosynthesis of amino acids.

9
Properties of amino acids due to amino group
◼ Sanger’s reaction. This reaction with Sanger’s reagent
produces a yellow-colored derivative, DNB-amino acid.
This reaction is used to detect concentration of amino acids
in solutions. It frees the N-terminal amino acid in a
polypeptide, thus this reaction is used in protein sequencing.
Remember the equation: AA-NH2 + Sanger’s reagent = DNB + HF
and the practical application of this reaction.

10
Properties due to amino group + carboxyl group
◼ Peptide bonding

11
◼ Ninhydrin reaction. Oxidative decarboxylation of -
amino acids.
Oxydized ninhydrin creates with the liberated NH3 a blue-
colored Rhumann’s complex. It is a very sensitive reaction
used in analytic chemistry for detection of amino acids
Remember the application of this reaction.

12
◼ Zwitterions. The name zwitter is derived from the German
word which means “hybrid”. Zwitterion (or) dipolar ion is
a hybrid molecule containing positive & negatively ionic
groups with the overall charge equal to zero. Basically, one
proton is transferred from the carboxyl group to the amino
group of self molecule at normal pH cellular levels.

Exercise 1
13
• Select a functional group that explains the
ability of amino acids to interact with alkali
ability of amino acids to interact with
Sanger’s reagent
ability of amino acids to interact with
alcohols

Exercise 2
14
Sanger reaction is shown in this scheme. Select all correct statements
regarding its practical applicability:
• Used in protein sequencing;
• Allows precipitating of amino acids by creating
insoluble salts with them;
• Allows measuring of concentrations of amino acids
in solutions by color intensity;
• Block carboxyl groups of amino acids to prevent
any other chemical reactions with them.
1
–1
1
–1

Chirality of amino
acids
15
◼ Optical properties. All amino acids except for glycine
exist in the form of two or more optical isomers due to the
presence of asymmetric α-carbon atoms.

Stereochemistry of amino acids
16
Imagine a mirror reflection of any 3D object
In many cases, mirror images can be superimposed over the original image by
rotation, for example: this solid-colored coffee mug:
In other cases, the mirror reflection cannot be superimposed on the initial image.
Both images are related as the right-handed to the left-handed ones, for example,
look at this coffee mug with a printed text:
Achiral objects – those ones which
are superimposable by rotation
on their mirror reflections.
Chiral objects – those ones which
are not superimposable by rotation
on their mirror reflections, but can be
(or cannot be) superimposable by
mirror reflection (enantiomers).
right-handed left-handed

17
A chiral C-atom (chiral centre) in a molecule is such one that is attached to
4 different chemical groups (radicals). One molecule may have several chiral centres.
Achiral objects – those ones which
can be superimposed on their
mirror reflections by rotation.
Chiral objects – those ones which
cannot be superimposable on their
mirror reflections by rotation.
Stereoisomers – molecules of the
same chemical structure, which differ
from each other only by their 3D
configuration; also called optical
isomers.
Enantiomers – pairs of
stereoisomers, which can be
superimposed by mirror reflection.

18
One chiral centre renders 2 optical stereoisomers, which are
mirror reflections of each other (enantiomers).
The maximum number of stereoisomers that one molecule has
is 2n, where n is the number of chiral centres.
A molecule with three chiral centres has 23=8 stereoisomers,
or 4 pairs of enantiomers.
Enantiomers – pairs of stereoisomers, which can be
superimposed by a mirror reflection. Each stereoisomer
always has one enantiomer. Total number of pairs of
enantiomers is 2(n-1), where n is the number of chiral centres.
The majority of the natural amino acids, except for glycine,
isoleucine and threonine, are enantiomers having L- and D-
stereoisomers.

19
-Carbon of all amino acids except for
glycine is a chiral centre rendering a
pair of enantiomers (L- and D-
stereoisomers).
All amino acids found in proteins are L-
stereoisomers; D-amino acids may be
found is several natural products
synthesized by non-ribosomal
polypeptide synthetases (NRPS) and in
cell walls of bacteria.
Glycine

20
Special nomenclature has been proposed by Fisher (1891) to specify the
absolute configuration of the four substituents attached to the chiral
carbon atom termed also D,L system for levorotatory (rotating polarized
light to the left) and dextrorotatory (to the right) glyceraldehyde.
Stereochemical isomers with the same spatial orientation of functional groups regarding the
aldehyde/carboxyl groups at the chiral centre as in L-glyceraldehyde are termed L-stereo-
isomers. However, not all L-amino acids are levorotatory and the actual direction of light
rotation can very with amino acid depending on its particular electronic and chemical
structure in ways that are hard to predict.

21
Bonds going
behind the plane
Meaning of the solid and dashed wedges in the absolute configuration
images
Bonds going
upward from the plane
This is a correct absolute
configuration of D-alanine
This is also D-alanine,
however the configuration is
not standard

Exercise 3
22
Complete the absolute configuration structure of the given amino
acids by using the provided radicals:
A) D-Alanine:
B) L-Alanine:
C) L-Alanine:
D) D-Ornithine:
–H
–NH3
+
–COO–
–CH3
–CH2-C6H5
–CH2-CH2-CH2-CH2-NH2
–CH2-CH2-CH2-NH2
–CH2-SH
–CH2-CH2-S-CH3
Radicals:

Exercise 4
23
An absolute configuration of citrulline is show below. Explain, is it D- or L-
optical isomer?
This is L-amino acid

How many are there optical
isomers of isoleucine?
24
There are 4 optical isomers of
Isoleucine, but only one form can be
found in nature: L-isoleucine:
The enantiomer of this stereoisomer
is D-isoleucine:
Two other enantiomers can be
synthesized: L-allo-isoleucine and
D-allo-isoleucine:
L D
L-allo- D-allo-

How many are there optical
isomers of threonine?
25
There are 4 optical isomers of
threonine, but only one form can be found
in proteins: L-threonine:
The enantiomer of this stereoisomer
is D-threonine:
Two other enantiomers can be
synthesized: L-allo-threonine and
D-allo-threonine:

Take-home messages
26
The general structure of amino acids consists of a carbon centre and its
four substituents: amino group (NH2 → NH3
+), carboxyl group (COOH →
COO−), a hydrogen atom (H), and a side radical, that determines individual
chemical properties of each amino acid.
The first three groups are common for all amino acids.
The basic amino acid structure is R-CH(NH2)-COOH → NH3
+-RCH-COO−
(remember the definition of zwitterion).
All -amino acids except for glycine have two or more optical (stereo-)
isomers:

Take-home messages
27
➢ Amino acids have several common chemical properties as all of them
comprise one -carboxyl and one -amino groups.
Due to amino group Due to carboxyl group
• Salt formation with mineral acids
• Reaction with benzaldehyde
• Sanger’s color reaction
• Salt formation with bases
• Reaction with alcohols
• Reaction with amines
• Decarboxylation
Due to amino group + carboxyl group
• Ninhydrin color reaction
• Zwitterion formation
➢ All amino acids except for glycine possess optical isomers due to the
presence of asymmetric α-carbon atoms. Majority of amino acids have
only one pair of enantiomers: L- and D-isomers; but isoleucine and
threonine have two pairs of enantiomers.
➢ All proteinogenic amino acids are L-stereoisomers.

Lecture 1 - General Properties of Amino Acids(2) (1).pdf

Recomendados

Recomendados

Más contenido relacionado

Similar a Lecture 1 - General Properties of Amino Acids(2) (1).pdf

Similar a Lecture 1 - General Properties of Amino Acids(2) (1).pdf (20)

Último

Último (20)

Lecture 1 - General Properties of Amino Acids(2) (1).pdf